Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma

April 14, 2026 updated by: Memorial Sloan Kettering Cancer Center

A Phase II Trial of Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma

The purpose of this study is to find out what effects, good and/or bad, the combination of irinotecan and temozolomide has on Ewing sarcoma.

Irinotecan and temozolomide are chemotherapy drugs that are used very often to treat pediatric patients at MSKCC. The investigators have used these two drugs for many years to treat patients with Ewing sarcoma whose cancer has relapsed.

For patients with newly diagnosed Ewing sarcoma the current standard of care at MSKCC is a five drug chemotherapy regimen in combination with surgery and/or radiation therapy. This standard regimen is called the EFT regimen. . Some patients with Ewing sarcoma do not have their cancer cured by the chemotherapy and surgery/radiation therapy.

This study adds the chemotherapy drugs called irinotecan and temozolomide to the standard EFT regimen. The investigators are trying to improve the success of standard therapy by adding these drugs. The use of irinotecan and temozolomide in this study is experimental because they have not been used before in patients with newly diagnosed Ewing sarcoma. However the investigators have found these drugs to be effective in patients with relapsed Ewing sarcoma. It is not known if adding these two drugs will improve the outcomes of patients treated for Ewing sarcoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

83

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Cancer Center Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age greater than or equal to one year and less than or equal to 40 years at the time of diagnosis
  • Newly diagnosed, previously untreated patients with histologically or molecularly confirmed Ewing sarcoma
  • Adequate hematologic function:
  • Absolute neutrophil count ≥ 1,000/K/mcl
  • Platelet count ≥ 100,000/Kmcl
  • Adequate renal function:
  • Normal creatinine for age (See table below) OR
  • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 Age(Years) Maximum Serum Creatinine (mg/dL) ≤ 5 0.8 6 to ≤ 10 1 11 to ≤ 15 1.2 ≥ 16 1.5

Adequate hepatic function:

  • Total bilirubin ≤ 1.5 x the ULN
  • AST ≤ 2.5 x the ULN [in the absence of hepatic involvement of tumor. Patients with hepatic involvement are considered eligibile for study]
  • ALT ≤ 2.5 x the ULN [in the absence of hepatic involvement of tumor. Patients with hepatic involvement are considered eligibile for study]

Normal cardiac function:

  • Shortening fraction ≥ 28% by echocardiogram OR
  • Left ventricular ejection fraction (LVEF) ≥ 50% on technetium- 99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram
  • Patients must consent to an indwelling central venous catheter.
  • Sexually active patients of reproductive potential must be willing to use an effective method of contraception.

Exclusion Criteria:

  • Prior chemotherapy or radiotherapy (other than limited, emergent radiotherapy for treatment of eg. spinal cord compromise or threatened airway)
  • Pregnant or breastfeeding females

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with localized disease

Patients with localized disease will receive six cycles of the combination as "maintenance" therapy following standard chemotherapy.

  • Cycles 4-6 will include:

    • Ifosfamide 2,800 mg/m2/day on days 1-5
    • Etoposide 100 mg/m2/day on days 1-5

  • Cycle 7 will include :

    • Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients < 10 years of age at a dose of 70 mg/kg/day
    • Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day
    • Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)

  • Cycles 8-13 will include:

    • Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously
    • Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously
Drug: Temozolomide
Drug: Cyclophosphamide
Drug: Vincristine
Procedure: Surgery
Drug: Irinotecan
Drug: Ifosfamide
Device: Doxorubicin
Drug: Etoposide
Radiation: Radiation Therapy*
If local control includes RT, RT should be given concurrently with chemotherapy cycles
Drug: Mesna
Mesna 2,100 mg/m2 (or 70 mg/kg if < 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.
Drug: Dexrazoxane
Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.
Drug: G-CSF
G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.
Experimental: Patients with metastatic disease

Patients will get 10 cycles of the combination intercalated between the final 4 cycles of standard chemotherapy.

  • Cycles 4, 5, 7, 8, 10, 11, 13, 14, 16, and 17 will include:

    • Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously
    • Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously

  • Cycles 6, 9, and 12 will include:

    • Ifosfamide 2,800 mg/m2/day on days 1-5
    • Etoposide 100 mg/m2/day on days 1-5

  • Cycle 15 will include:

    • Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients < 10 years of age at a dose of 70 mg/kg/day
    • Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day
    • Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)
Drug: Temozolomide
Drug: Cyclophosphamide
Drug: Vincristine
Procedure: Surgery
Drug: Irinotecan
Drug: Ifosfamide
Device: Doxorubicin
Drug: Etoposide
Radiation: Radiation Therapy*
If local control includes RT, RT should be given concurrently with chemotherapy cycles
Drug: Mesna
Mesna 2,100 mg/m2 (or 70 mg/kg if < 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.
Drug: Dexrazoxane
Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.
Drug: G-CSF
G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
event free survival of patients with localized disease
Time Frame: 4 years

We will determine event free survival from the time of study entry for all patients. An event would include death from any cause, progression of tumor, recurrence of tumor, or second malignancy.

Progressive disease (PD) will be defined according to RECIST 1.1.
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
event free survival of patients with metastatic disease
Time Frame: 4 years

We will determine event free survival from the time of study entry for all patients. An event would include death from any cause, progression of tumor, recurrence of tumor, or second malignancy.

Progressive disease (PD) will be defined according to RECIST 1.1.
4 years
adverse event profile
Time Frame: 2 years
Toxicities are graded by the Common Toxicity Criteria (Version 4.0) developed by the National Cancer Institute (NCI) of the USA.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Investigators

  • Principal Investigator: Emily Slotkin, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

May 23, 2013

First Submitted That Met QC Criteria

May 28, 2013

First Posted (Estimated)

May 29, 2013

Study Record Updates

Last Update Posted (Actual)

April 17, 2026

Last Update Submitted That Met QC Criteria

April 14, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-068

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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